Primary infection with varicella-zoster virus (VZV) causes chickenpox, and reactivation of the virus from latency results in zoster. The purpose of this project is to study the molecular basis for latency of VZV and for attenuation of the Oka vaccine strain of VZV.We have developed a small animal model for VZV latency by infecting neonatal rats with the virus. These animals become latently infected, and analysis of the their nervous system shows viral DNA is present 6 weeks after infection. A VZV gene (ORF21) that has been associated with latent infection in humans is expressed 6 weeks after infection, while another gene (ORF40) not associated with latency is not expressed. To begin to understand the molecular basis for attenutation of the Oka vaccine strain of VZV, we have sequenced a large portion of the Oka vaccine strain and compared it to the sequence of the parental (wild-type) Oka strain. Several differences were noted in one VZV gene (ORF62)and tests based on differences in this gene successfully distinguished the Oka vaccine strain from its wild-type parent. These changes remained stable after passage of the virus in humans.